Marcus A. Tius, PhD, MS
- University of Hawaii Cancer Center Special Liaison to
University of Hawaii at Manoa
- Joanna L. Sullivan Distinguished Professor in Cancer Research
University of Hawaii Cancer Center
- Associate Member
Cancer Biology Program
University of Hawaii Cancer Center
Chemistry, College of Natural Sciences, University of Hawaii at Manoa
- PhD, MS, Chemistry
The focus of the research is in the area of organic synthesis, much of which has a cancer focus. Organic synthesis plays a pivotal role in drug discovery and also provides many of the tools for probing the molecular mechanisms of biochemical pathways. Most chemotherapeutic agents in current use against cancer are semisynthetic (e.g. taxol) or are completely synthetic (e.g. 5-fluorouracil). Even when the initial lead compound is a natural product, as it is in the case of taxol, the optimal drug often requires one or more chemical modifications. Organic synthesis is always required to determine the structural features of a drug molecule that are essential for activity, and is often necessary to elucidate the mechanism of action.
The Tius group does several kinds of research. (1) New methods development for efficient synthesis of natural products; (2) Application of these methods to the synthesis of natural products that have some cancer-relevant activity; (3) Collaboration with medicinal chemists and cancer biologists to develop new synthetic small molecules that may serve as leads for drug development. Areas of special interest are the synthesis and medicinal chemistry of cannabinoids, primarily classical-nonclassical hybrid structures, and the development of new versions of the Nazarov cyclization. A long-term collaboration with Dr. Alex Makriyannis (Director, Center for Drug Discovery, Northeastern University) has resulted in the discovery of new, selective, small molecule cannabinoid ligands. The CB2 cannabinoid receptor is implicated in immune regulation and CB2 antagonists up-regulate myeloid-derived suppressor cells leading to tumor suppression.
A scale-able synthesis of both enantiomers of rocaglamide, a plant-derived cytostatic small molecule, was recently completed making use of a palladium-catalyzed asymmetric cyclization reaction developed within the Tius group. Other variants of the asymmetric Nazarov cyclization discovered in the Tius group reaction have been used to prepare terpestacin, an anti-angiogenic natural product, and also a series of analogs.The Tius group collaborates with the groups of Dr. Joe Ramos (UH Cancer Center, rocaglamide) and Dr. James Turkson (UH Cancer Center, STAT3 inhibitors).
- Yue P, Lopez-Tapia F, Paladino D, Li Y, Chen C-H, Namanja A T, Hilliard T, Chen Y, Tius MA, Turkson J. (2016). Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo. Cancer Res, 76, 652 - 663. DOI:10.1158/0008-5472.CAN-14-3558.
- Zhou Z, Dixon D, Jolit A, Tius MA. (2016). The Evolution of the Total Synthesis of Rocaglamide. Chem Eur J, 22, 15929 â€“ 15936. DOI: 10.1002/chem.201603312.
- Asari A, Lam Y, Tius M, Houk K. (2015). Origins of the Stereoselectivity in a Thioureaâ€“Primary Amine-catalyzed Nazarov Cyclization. J Am Chem Soc, 137, 13191 - 13199.
- Zhou Z, Tius MA. (2015). Synthesis of Each Enantiomer of Rocaglamide by Means of a Pd(0)-Catalyzed Nazarov-Type Cyclization. Angew Chem Int Ed, 54, 6037-6040. DOI: 10.1002/anie.201501374R1.
- Kitamura K, Shimada N, Stewart C, Atesin A, AteĹźin TA, Tius MA. (2015). Enantioselective Palladium(0)-Catalyzed Nazarov-type Cyclization. Angew Chem Int Ed, 54, 6288-6291. DOI: 10.1002/anie.201500881R1.
- Ogawa G, Zhou H, Nikas SP, Halikhedkar A, Mallipeddi S, Tius MA, Makriyannis A. (2015). 3'-Functionalized Adamantyl Cannabinoid Receptor Probes. J Med Chem, 58, 3104-3116.
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